Phase response curves for home remedies to treat circadian misalignment

治疗昼夜节律失调的家庭疗法的相位响应曲线

• 批准号: 7797510
• 负责人: CHARMANE I EASTMAN
• 金额: $ 37万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-05 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7797510
• 关键词: Advanced Sleep Phase Syndrome; Advertisements; Beds; Birds; Body Temperature; Boxing; Chronic Insomnia; Circadian Rhythms; Clinic; Delayed Sleep Phase Syndrome; Distress; Dose; Elderly; Future; General Population; Home Remedy; Home environment; Human; Industry; Jet Lag Syndrome; Light; Measures; Melatonin; Middle Insomnia; Outpatients; Patients; Phase; Phase response curves; Photoreceptors; Principal Investigator; Protocols documentation; Recommendation; Relative (related person); Running; Schedule; Schools; Seasonal Affective Disorder; Shapes; Shift-Work Sleep Disorder; Sleep; Sleep Deprivation; Sleep Disorders; Sleep Wake Cycle; Societies; Stimulus; Strigiformes; Symptoms; System; Testing; Time; Travel; Vertebrate Photoreceptors; Work; alertness; base; circadian pacemaker; cost; gastrointestinal; innovation; light treatment; novel; pill; practical application; programs; response; shift work; sleep onset; young adult

DESCRIPTION (provided by applicant): In modern society, there are a number of situations in which human circadian rhythms are misaligned with the desired sleep/wake schedule. Jet travel, night shift work, early morning shift work and merely returning to a normal work or school schedule either on Monday morning after sleeping later on the weekend or after being on vacation can all result in circadian misalignment. This misalignment produces a wide range of symptoms including daytime sleepiness, decreased alertness, insomnia, chronic partial sleep deprivation, and gastrointestinal distress. Both bright light and melatonin are able to reset or phase shift the circadian clock, and have been used to help people adapt to their desired sleep/wake schedule. The commercial, over-the-counter availability of a wide range of melatonin doses and light boxes highlights the consumer's desire for simple, non-invasive, at-home treatments to treat circadian-related sleep disorders. Recently it has been demonstrated that the circadian system primarily detects light using a novel, blue-light-sensitive photoreceptor, although the rods and cones also provide some input. Industry has capitalized on this discovery, and blue light boxes are now available. However, in order to obtain maximum benefit from melatonin pills or light boxes it is essential to know their optimal administration time. Phase response curves (PRCs) describe the phase shifting response to a specific stimulus when it is presented at different times throughout the 24-h day. We propose to generate PRCs to over-the-counter, commercially available phase shifting products: melatonin pills and light boxes. Therefore, the results of our studies will yield direct practical recommendations. We will generate 4 PRCs: 1) 0.5 mg melatonin, 2) 3.0 mg melatonin, 3) bright white light, and 4) medium intensity blue light. We will use a novel, efficient protocol in which subjects free-run through an ultradian light-dark/wake-sleep schedule (4 h days), and we will apply melatonin or light at various points throughout the circadian cycle. We will use the endogenous melatonin rhythm as a marker of the circadian clock, to calculate phase shifts and the time of the administration of the melatonin or light. The PRCs will tell us when to administer these phase shifting stimuli to achieve the maximum phase shift in the desired direction, and also times at which use of these products would induce a phase shift in the wrong direction and should be avoided. This information is needed so that professionals can make the best recommendations to patients and other consumers. In addition, comparison of the PRCs may also reveal information about the human circadian system, such as the relative phase shifting abilities of melatonin and light or the relative contribution of photoreceptors to the circadian system.

描述（由申请人提供）：在现代社会中，存在许多人类昼夜节律与期望的睡眠/觉醒时间表不一致的情况。喷气式飞机旅行，夜班工作，清晨轮班工作，以及仅仅在周末晚些时候睡觉后或度假后的周一早上恢复正常的工作或学校时间表，都可能导致昼夜节律失调。这种失调产生了广泛的症状，包括白天嗜睡、警觉性下降、失眠、慢性部分睡眠剥夺和胃肠道不适。明亮的光线和褪黑激素都能够重置或相移生物钟，并已被用来帮助人们适应他们想要的睡眠/觉醒时间表。商业，非处方的各种褪黑激素剂量和灯箱的可用性突出了消费者对简单，非侵入性，家庭治疗来治疗昼夜节律相关的睡眠障碍的需求。最近已经证明，昼夜节律系统主要使用一种新的蓝光敏感的光感受器来检测光，尽管视杆细胞和视锥细胞也提供一些输入。工业界利用了这一发现，现在可以使用蓝光盒。然而，为了从褪黑激素药丸或灯箱中获得最大益处，必须知道它们的最佳给药时间。相位响应曲线（PRC）描述了在24小时内的不同时间对特定刺激的相移响应。我们建议将PRC生成为非处方的市售相移产品：褪黑激素药丸和灯箱。因此，我们的研究结果将产生直接的实际建议。我们将产生4个PRC：1）0.5 mg褪黑激素，2）3.0 mg褪黑激素，3）明亮的白色光，以及4）中等强度的蓝光。我们将使用一种新的，有效的协议，其中受试者自由运行通过ultradian光暗/唤醒睡眠时间表（4小时天），我们将在整个昼夜节律周期的各个点应用褪黑激素或光。我们将使用内源性褪黑激素节律作为生物钟的标记，以计算相移和褪黑激素或光的施用时间。PRC将告诉我们何时给予这些相移刺激以在所需方向上实现最大相移，以及使用这些产品会在错误方向上引起相移并应避免的时间。需要这些信息，以便专业人员能够向患者和其他消费者提供最佳建议。此外，PRC的比较还可以揭示关于人类昼夜节律系统的信息，例如褪黑激素和光的相对相移能力或光感受器对昼夜节律系统的相对贡献。